Christmas holiday round-up

Against the odds, and going into the uncertainty of a 2024 US presidential election, biotechnology ended last year on a high. After standing off 15% year to date in late October the iShares biotechnology index mounted a comeback, driven in part by deal making, to end 2023 up 4%.

Business development remained buoyant during the Christmas period, most notably seeing RayzeBio and Gracell fall to takeovers, while project licensing deals were struck by Johnson & Johnson and Astellas. But it wasn’t all good news, with Amgen’s Lumakras receiving a US complete response letter, and Iovance and Oncternal reporting patient deaths with key assets.

Another TROP2 deal

J&J’s deal was struck with the South Korean company LegoChem, and concerned the TROP2-targeted antibody-drug conjugate LCB84, which is the subject of a North American phase 1/2 clinical trial. For $100m up front, plus a potential $200m option exercise fee, J&J gained worldwide development and commercialisation rights.

This followed numerous tie-ups in the TROP2 ADC space, including Daiichi Sankyo/AstraZeneca’s collaboration for datopotamab deruxtecan, Merck & Co’s deal with Kelun for sacituzumab tirumotecan, and Gilead’s $21bn acquisition of Immunomedics, which brought Trodelvy. Last August BioNTech bought ex-China rights to DualityBio’s DB-1305.

Less positive news was forthcoming from Iovance, which has been dogged by delays for its tumour-infiltrating lymphocyte project lifileucel in melanoma; investors got another nasty surprise last week after the therapy was put on hold in non-small cell lung cancer, where the TIL asset is known as LN-145.

The hold came after a patient death in the IOV-LUN-202 trial that Iovance said could have been related to the preconditioning regimen; the company also told Mizuho analysts that the death had been deemed due to disease progression. Iovance’s backers will have to hope this won’t affect lifileucel in melanoma, where an FDA approval decision is due by 24 February. The company is worth $2bn, so has much to prove.

Iovance’s TIL timeline

Source: OncologyPipeline.

Not put on clinical hold, but surely now at risk of having one imposed, was the micro cap Oncternal, which recently switched its work on ROR1 blockade away from the MAb zilovertamab and towards the Car-T therapy ONCT-808.

A clinical trial update revealed that all three refractory B-cell lymphoma patients given 1 million ONCT-808 cells achieved metabolic responses. However, the first subject to receive a higher dose, 3 million cells, died of a cytokine release and neurotoxicity-related adverse event; Oncternal proposes to modify protocol eligibility criteria, and to test lower ONCT-808 doses in future.

Lumakras CRL

Amgen got an unwanted Christmas gift in the form of an FDA complete response letter for Lumakras. The group had been seeking full approval for the drug, which already has an accelerated nod for KRAS G12C-mutated second-line lung cancer.

The FDA’s decision is not surprising after Lumakras’s confirmatory trial, Codebreak-200, was savaged by an adcom last year. But, in an unusual twist, the agency is asking for another confirmatory study to be completed by February 2028. Lumakras’s marketed status looks safe, for now, but a lot will depend on this future trial.

Finally, there was good news for the private US biotech Elpiscience, which got $37m in up-front and option licence fees from Astellas in a collaboration encompassing bispecific macrophage engagers, ES019 (a SIRPα x PD-L1 BITE) and an undisclosed programme. Like ADCs, bispecifics have been the subject of significant recent deal making.